| Kornberg Associates | Architects Completes UC Riverside Stem Cell Core Facility Project
December 10, 2009 at 7:53 pm
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| CIRM Identifies Training Grant Recipients
December 10, 2009 at 5:53 pm
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| | The California stem cell agency has identified the recipients of the $10.8 million in training grants. They include: The Buck Institute, USC, California State University campuses at Fullerton, Northridge and San Bernardino and city colleges in Berkeley and San Francisco. Here is a link to the CIRM news release. |
| Trend Sourcing Additional Acquisitions and Opportunities From the Bio R& amp;D Industries, Such as Stem Cell Research and Ultrasound Dentistry Technology
December 10, 2009 at 5:52 pm
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| Torres Receives $225,000 Salary as CIRM Vice Chair
December 10, 2009 at 5:18 pm
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| | Directors of the California stem cell agency this afternoon unanimously approved a $225,000 salary for one of its co-vice chairmen, Art Torres, declaring that his work was "extraordinary" and has helped to improve relations in the nation's capital and elsewhere.Torres (at right) joined CIRM in March on a half-time basis, with a $75,000 salary. Today's action gives him a $150,000 boost for work on |
| Prop. 71 Not Alone in Super, Super Majority Requirement
December 10, 2009 at 2:52 pm
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| | The outside counsel for the California stem cell agency today pointed out that other adopted ballot measures besides Prop. 71 require a super, supermajority vote to be altered by the state Legislature.James Harrison, of the Remcho, Johansen & Purcell firm of San Leandro, Ca., made the comment via email in connection with our "Legal Cap" item Dec. 9, 2009.He said, "I noticed that you said that no |
| Successful Stem Cell Therapy for Treatment of Eye Disease
December 10, 2009 at 1:51 pm
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| New ethical questions are being raised in stem cell research
December 10, 2009 at 1:51 pm
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| CIRM Pumps More Millions Into Training
December 10, 2009 at 1:26 pm
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| | Directors of the California stem cell agency today added $10.8 million to its training efforts at California colleges and universities, a welcome change for the institutions that have been reeling under brutal cuts because of the state's financial situation. Earlier this year, the directors declined to fund the seven programs because of CIRM's then precarious financial situation. However, the |
| Correction
December 10, 2009 at 1:06 pm
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| | An earlier version of the "Keirstead Leaves" item said that Hans Keirstead and CIRM Chairman Robert Klein briefed Congress on stem cell research last March. It was, in fact, another Robert Klein. |
| Successful stem cell therapy for treatment of eye disease
December 10, 2009 at 12:51 pm
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| Keirstead Leaves Co-Directorship at UC Irvine Stem Cell Center
December 10, 2009 at 11:36 am
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| | A California scientist who has been a media star and super-salesman for human embryonic stem cell research has quietly stepped down as co-director of the stem cell research center at UC Irvine.The announcement of Hans Keirstead's resignation was made Nov. 24 in an internal UCI email by Susan Bryant, vice chancellor for research at the campus. She said that Keirstead (at left) was resigning as |
| Hebrew University, American researchers show 'trigger' to stem cell differentiation
December 10, 2009 at 10:51 am
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| Stem Cell Therapeutics Corp. Announces Additional U.S. Patent
December 10, 2009 at 9:50 am
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| Differential Destruction of Stem Cells: Implications for Targeted Cancer Stem Cell Therapy.
December 10, 2009 at 6:57 am
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| | Differential Destruction of Stem Cells: Implications for Targeted Cancer Stem Cell Therapy. Cancer Res. 2009 Dec 8; Authors: Sehl ME, Sinsheimer JS, Zhou H, Lange KL Cancer stem cells represent a novel therapeutic target. The major challenge in targeting leukemic stem cells (LSC) is finding therapies that largely spare normal hematopoietic stem cells (HSC) while eradicating quiescent LSCs. We present a mathematical model to predict how selective a therapy must be to ensure that enough HSCs survive when LSCs have been eradicated. Stem cell population size is modeled as a birth-death process. This permits comparison of LSC and HSC eradication times under therapy and calculation of the number of HSCs at the time of LSC eradication for varied initial population sizes and stem cell death rates. We further investigate the effects of LSC quiescence and resistance mutations on our predictions. From a clinical point of view, our models suggest criteria by which cancer stem cell therapy safety can be assessed. We anticipate that in conjunction with experimental observation of cancer stem cell killing rates, our results will be useful in screening targeted therapies for both hematologic and solid tumor malignancies. [Cancer Res 2009;69(24):9481-9]. PMID: 19996291 [PubMed - as supplied by publisher] |
| Adipose tissue: a new source for cardiovascular repair.
December 10, 2009 at 6:56 am
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| | Adipose tissue: a new source for cardiovascular repair. J Cardiovasc Med (Hagerstown). 2009 Dec 7; Authors: Madonna R, De Caterina R Along with angiogenesis and gene therapy, stem cell transplantation is one of the newest treatment modalities proposed to improve the outcome of patients with heart failure or infarction. In this context, much interest has stemmed from experimental studies showing that cardiac transfer of unfractionated or partially purified bone marrow cells, or stem cells and progenitor cells derived from the bone marrow or peripheral blood, can enhance functional recovery after an acute myocardial infarction. On the basis of these data, stem cells and progenitor cells derived from the bone marrow have been proposed for use in the repair of cardiac tissue after acute myocardial infarction in patients. However, the relatively low abundance, small tissue volume, difficult accessibility and disease-related malfunction of bone marrow-derived stem cells make their clinical usefulness difficult in some situations. Recently it has been shown that adipose tissue contains a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that, in cell culture conditions, have extensive proliferative capacity and are able to differentiate into several lineages, including endothelial cells, smooth muscle cells and cardiomyocytes. The similarities between stem cells extracted from the bone marrow and the adipose tissue suggest the potential for the adipose tissue to act as an alternative, and perhaps preferable, cell source for repairing damaged tissues, such as the ischemic or infarcted heart.In this review we discuss molecular and functional characterization, preclinical results and currently ongoing clinical trials using adipose-derived stem cells in cardiovascular repair. PMID: 19996982 [PubMed - as supplied by publisher] |
| Isolation, characterization and differentiation potential of canine adipose-derived stem cells.
December 10, 2009 at 6:56 am
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| | Isolation, characterization and differentiation potential of canine adipose-derived stem cells. Cell Transplant. 2009 Dec 8; Authors: Vieira N, Brandalise V, Zucconi E, Secco M, Strauss B, Zatz M Adipose tissue may represent a potential source of adult stem cells for tissue engineering applications in veterinary medicine. It can be obtained in large quantities, under local anesthesia and with minimal discomfort. In this study, canine adipose tissue was obtained by biopsy from subcutaneous adipose tissue or by suction-assisted lipectomy (i.e., liposuction). Adipose tissue was processed to obtain a fibroblast-like population of cells similar to human Adipose Derived Stem (hASC) cells. These canine Adipose-derived Stem Cells (cASCs) can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of cASCs are of mesodermal or mesenchymal origin. cASCs are able to differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirate, canine adipose tissue may also contain multipotent cells and represent an important stem cell source both for veterinary cell therapy as well as preclinical studies. PMID: 19995482 [PubMed - as supplied by publisher] |
| Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.
December 10, 2009 at 6:05 am
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| | Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells. Glia. 2009 Dec 8; Authors: Huang J, Ye Z, Hu X, Lu L, Luo Z Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering. (c) 2009 Wiley-Liss, Inc. PMID: 19998481 [PubMed - as supplied by publisher] |
| Effect of recombinant galectin-1 on the growth of immortal rat chondrocyte on chitosan-coated PLGA scaffold.
December 10, 2009 at 6:05 am
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| | Effect of recombinant galectin-1 on the growth of immortal rat chondrocyte on chitosan-coated PLGA scaffold. J Biomed Mater Res A. 2009 Dec 8; Authors: Chen SJ, Lin CC, Tuan WC, Tseng CS, Huang RN The effect of galectin-1 (GAL1) on the growth of immortal rat chondrocyte (IRC) on chitosan-modified PLGA scaffold is investigated. The experimental results showed that water absorption ratio of chitosan-modified PLGA scaffold was 70% higher than that of PLGA alone after immersion in ddH(2)O for 2 weeks, indicating that chitosan-modification significantly enhances the hydrophilicity of PLGA. The experimental results also showed that GALl efficiently and spontaneously coats the chitosan-PLGA scaffold surface to promote adhesion and growth of immortal rat chondrocyte (IRC). To investigate the effect of endogenous GAL1, the full-length GAL1 cDNAs were cloned and constructed into pcDNA3.1 vectors to generate a plasmid expressed in IRC (IRC-GAL1). The results showed that IRC-GAL1 growth was significantly higher than that of IRC on chitosan-PLGA scaffold. The GAL1-potentiated IRC growth on chitosan-PLGA scaffold was dose-dependently inhibited by TDG (specific inhibitor of GAL1 binding). These results strongly suggest that GAL1 is critical for enhancing IRC cell adhesion and growth on chitosan-PLGA scaffold. Moreover, GAL1-coating or expression tends to promote IRC cell-cell aggregation on chitosan-PLGA scaffold and significantly enhances IRC migration. These results suggest that GAL1 probably could induce tissue differentiation and facilitates cartilage reconstruction. In conclusion, the experimental results suggest that both GAL1 and chitosan are important for enhancing IRC cell adhesion and growth on PLGA scaffold, and GAL1 is a potential biomaterial for tissue engineering. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID: 19998464 [PubMed - as supplied by publisher] |
| Micropatterned three-dimensional hydrogel system to study human endothelial-mesenchymal stem cell interactions.
December 10, 2009 at 6:05 am
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| | Micropatterned three-dimensional hydrogel system to study human endothelial-mesenchymal stem cell interactions. J Tissue Eng Regen Med. 2009 Dec 8; Authors: Trkov S, Eng G, Di Liddo R, Parnigotto PP, Vunjak-Novakovic G The creation of vascularized engineered tissues of clinically relevant size is a major challenge of tissue engineering. While it is known that endothelial and mural vascular cells are integral to the formation of stable blood vessels, the specific cell types and optimal conditions for engineered vascular networks are poorly understood. To this end, we investigated the vasculogenic potential of human mesenchymal stem cell (MSC) populations derived from three different sources: (a) bone marrow aspirates; (b) perivascular cells from the umbilical cord vein; and (c) perivascular cells from the umbilical cord artery. Cell populations were isolated and identified as MSCs according to their phenotypes and differentiation potential. Human umbilical vein endothelial cells (HUVECs) were used as a standard for endothelial cells. A novel co-culture system was developed to study cell-cell interactions in a spatially controlled three-dimensional (3D) fibrin hydrogel model. Using microfluidic patterning, it was possible to localize hydrogel-encapsulated HUVECs and MSCs within separate channels spaced at 500, 1000 or 2000 microm. All three MSC populations had similar expression profiles of mesenchymal cell markers and similar capacity for osteogenic and adipogenic differentiation. However, bone marrow-derived MSCs (but not umbilical vein or artery derived MSCs) showed strong distance-dependent migration toward HUVECs and supported the formation of stable vascular networks resembling capillary-like vasculature. The presented approach provides a simple and robust model to study the cell-cell communication of relevance to engineering vascularized tissues. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 19998330 [PubMed - as supplied by publisher] |
| Passaged human chondrocytes accumulate extracellular matrix when induced by bovine chondrocytes.
December 10, 2009 at 6:05 am
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| | Passaged human chondrocytes accumulate extracellular matrix when induced by bovine chondrocytes. J Tissue Eng Regen Med. 2009 Dec 8; Authors: Ahmed N, Taylor DW, Wunder J, Nagy A, Gross AE, Kandel RA A source of sufficient number of cells is a major limiting factor for cartilage tissue engineering. To circumvent this problem, we developed a co-culture method to induce redifferentiation in bovine articular chondrocytes, which had undergone dedifferentiation following serial passage in monolayer culture. In this study we determine whether human osteoarthritic (OA) and non-diseased passaged dedifferentiated chondrocytes will respond similarly. Human passaged chondrocytes were co-cultured for 4 weeks with primary bovine chondrocytes and their redifferentiation status was determined. Afterwards the cells were cultured either independently or in co-culture with cryopreserved passaged cells for functional analysis. The co-culture of passaged cells with primary chondrocytes resulted in reversion of their phenotype towards articular chondrocytes, as shown by increased gene expression of type II collagen and COMP, decreased type I collagen expression and extracellular matrix formation in vitro. Furthermore, this redifferentiation was stable, as those cells not only formed hyaline-like cartilage tissue when grown on their own but also they could induce redifferentiation of passaged chondrocytes in co-culture. These data suggest that it may be possible to use autologous chondrocytes obtained from osteoarthritic cartilage to form tissue suitable to use for cartilage repair. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 19998328 [PubMed - as supplied by publisher] |
| Three Dimensional OCT in the Engineering of Tissue Constructs: A Potentially Powerful Tool for Assessing Optimal Scaffold Structure.
December 10, 2009 at 6:05 am
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| | Three Dimensional OCT in the Engineering of Tissue Constructs: A Potentially Powerful Tool for Assessing Optimal Scaffold Structure. Open Tissue Eng Regen Med J. 2009;2:8-13 Authors: Zheng K, Rupnick MA, Liu B, Brezinski ME Optical Coherence Tomography (OCT) provides detailed, real-time information on the structure and composition of constructs used in tissue engineering. The focus of this work is the OCT three-dimensional assessment of scaffolding architecture and distribution of cells on it. PLGA scaffolds were imaged in two and three-dimensions, both seeded and unseeded with cells. Then two types of scaffolds were reconstructed in three dimensions. Both scaffolding types were examined at three different seeding densities. The importance of three-dimensional assessments was evident, particularly with respect to porosity and identification of asymmetrical cell distribution. PMID: 19997536 [PubMed - as supplied by publisher] |
| Neuronal Differentiation of PC12 Cells Cultured on Growth Factor-Loaded Nanoparticles Coated on PLGA Microspheres.
December 10, 2009 at 6:05 am
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| | Neuronal Differentiation of PC12 Cells Cultured on Growth Factor-Loaded Nanoparticles Coated on PLGA Microspheres. J Microbiol Biotechnol. 2009 Nov;19(11):1490-5 Authors: Park KH, Kim H, Na K The development of nanotechnology has penetrated the fields of biology and medicine, resulting in remarkable applications for tissue regeneration. In order to apply this technology to tissue engineering, we have developed nanoscaled 3D scaffolds consisting of growth factor-loaded heparin/poly(l-lysine) nanoparticles (NPs) attached to the surface of polymeric microspheres via polyionic complex methods. Growth factor-loaded NPs were simply produced as polyelectrolyte complexes with diameters of 100-200 nm. They were then coated onto positively charged poly(lacticco- glycolic acid) (PLGA) pretreated with polyethyleneimine to enable cell adhesion, proliferation, and stimulation of neurite outgrowth. Propidium iodide staining and beta-tubulin analysis revealed that neuronal PC12 cells proliferated extensively, expressed significant amounts of b-tubulin, and showed well-structured neurite outgrowth on polymeric microspheres by stimulation with growth factors. These results suggest that cellular adhesion and biological functionality on prepared PLGA microspheres enabled terminal differentiation of neuronal cells. PMID: 19996706 [PubMed - in process] |
| The regulation of tendon stem cell differentiation by the alignment of nanofibers.
December 10, 2009 at 6:05 am
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| | The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials. 2009 Dec 6; Authors: Yin Z, Chen X, Chen JL, Shen WL, Hieu Nguyen TM, Gao L, Ouyang HW Tendon is a specific connective tissue composed of parallel collagen fibers. The effect of this tissue-specific matrix orientation on stem cell differentiation has not been investigated. This study aimed to determine the effects of nanotopography on the differentiation of human tendon stem/progenitor cells (hTSPCs) and develop a biomimetic scaffold for tendon tissue engineering. The immuno-phenotype of fetal hTSPCs was identified by flow cytometry. The multipotency of hTSPCs toward osteogenesis, adipogenesis, and chondrogenesis was confirmed. Then, the hTSPCs were seeded onto aligned or randomly-oriented poly (l-lactic acid) nanofibers. Scanning electron micrographs showed that hTSPCs were spindle-shaped and well orientated on the aligned nanofibers. The expression of tendon-specific genes was significantly higher in hTSPCs growing on aligned nanofibers than those on randomly-oriented nanofibers in both normal and osteogenic media. In addition, alkaline phosphatase activity and alizarin red staining showed that the randomly-oriented fibrous scaffold induced osteogenesis, while the aligned scaffold hindered the process. Moreover, aligned cells expressed significantly higher levels of integrin alpha1, alpha5 and beta1 subunits, and myosin II B. In in vivo experiments, the aligned nanofibers induced the formation of spindle-shaped cells and tendon-like tissue. In conclusion, the aligned electrospun nanofiber structure provides an instructive microenvironment for hTSPC differentiation and may lead to the development of desirable engineered tendons. PMID: 19995669 [PubMed - as supplied by publisher] |
| Material Properties and Osteogenic Differentiation of Marrow Stromal Cells on Fiber-Reinforced Laminated Hydrogel Nanocomposites.
December 10, 2009 at 6:05 am
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| | Material Properties and Osteogenic Differentiation of Marrow Stromal Cells on Fiber-Reinforced Laminated Hydrogel Nanocomposites. Acta Biomater. 2009 Dec 5; Authors: Xu W, Ma J, Jabbari E The fibrils in the bone matrix are glued together by ECM proteins to form laminated structures (osteons) to provide elasticity and a supportive substrate for osteogenesis. The objective of this work was to investigate material properties and osteogenic differentiation of bone marrow stromal (BMS) cells seeded on osteon-mimetic fiber-reinforced hydrogel/apatite composites. Layers of electrospun poly(L-lactide) (L-PLA) fiber mesh coated with a poly(lactide-co-ethylene oxide fumarate) (PLEOF) hydrogel precursor solution were stacked and pressed together, and crosslinked to produce a laminated fiber-reinforced composite. Hydroxyapatite (HA) nanocrystals were added to the precursor solution to produce an osteoconductive matrix for BMS cells. Acrylamide-terminated RGD peptide (Ac-GRGD) was conjugated to the PLEOF/HA hydrogel phase to promote focal point adhesion of BMS cells. Laminates were characterized with respect to Young's modulus, degradation kinetics, and osteogenic differentiation of BMS cells. The moduli of the laminates under dry and wet conditions were significantly higher than those of the fiber mesh and PLEOF/HA hydrogel, and within the range of values reported for wet human cancellous bone. At days 14 and 21, ALPase activity of the laminates was significantly higher than those of the fiber mesh and hydrogel. Lamination significantly increased the extent of mineralization of BMS cells and laminates with HA and conjugated with RGD (Lam-RGD-HA) had 2.7-, 3.5-, and 2.8-fold higher calcium content (compared to laminates without HA or RGD) after 7, 14, and 21 days, respectively. The Lam-RGD-HA group had significantly higher expression of osteopontin (OP) and osteocalcin (OC) compared to the hydrogel or laminates without HA or RGD, consistent with the higher ALPase activity and calcium content of Lam-RGD-HA. Laminated osteon-mimetic structures have the potential to provide mechanical strength to the regenerating region as well as supporting the differentiation of progenitor cells to the osteogenic lineage. PMID: 19995620 [PubMed - as supplied by publisher] |
| Isolation, characterization and differentiation potential of canine adipose-derived stem cells.
December 10, 2009 at 6:05 am
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| | Isolation, characterization and differentiation potential of canine adipose-derived stem cells. Cell Transplant. 2009 Dec 8; Authors: Vieira N, Brandalise V, Zucconi E, Secco M, Strauss B, Zatz M Adipose tissue may represent a potential source of adult stem cells for tissue engineering applications in veterinary medicine. It can be obtained in large quantities, under local anesthesia and with minimal discomfort. In this study, canine adipose tissue was obtained by biopsy from subcutaneous adipose tissue or by suction-assisted lipectomy (i.e., liposuction). Adipose tissue was processed to obtain a fibroblast-like population of cells similar to human Adipose Derived Stem (hASC) cells. These canine Adipose-derived Stem Cells (cASCs) can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of cASCs are of mesodermal or mesenchymal origin. cASCs are able to differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirate, canine adipose tissue may also contain multipotent cells and represent an important stem cell source both for veterinary cell therapy as well as preclinical studies. PMID: 19995482 [PubMed - as supplied by publisher] |
| New Pulsatile Hydrostatic Pressure Bioreactor for Vascular Tissue-Engineered Constructs.
December 10, 2009 at 6:05 am
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| | New Pulsatile Hydrostatic Pressure Bioreactor for Vascular Tissue-Engineered Constructs. Artif Organs. 2009 Nov 26; Authors: Shaikh FM, O'Brien TP, Callanan A, Kavanagh EG, Burke PE, Grace PA, McGloughlin TM Abstract Mechanical conditioning represents a potential means to enhance the biochemical and biomechanical properties of tissue-engineered cell constructs. Bioreactors that can simulate physiologic conditions can play an important role in the preparation of tissue-engineered constructs. Although various forms of bioreactor systems are currently available, these have certain limitations, particularly when these are used for the creation of vascular constructs. The aim of the present report is to describe and validate a novel pressure bioreactor system for the creation of vascular tissue. Here, we present and discuss the design concepts, criteria, as well as the development of a novel pressure bioreactor. The system is compact and easily housed in an incubator to maintain sterility of the construct. Moreover, the proposed bioreactor, in addition to mimicking in vivo pressure conditions, is flexible, allowing different types of constructs to be exposed to various physiologic pressure conditions. The core bioreactor elements can be easily sterilized and have good ergonomic assembly characteristics. This system is a fundamental tool, which may enable us to make further advances in bioreactor technology and tissue engineering. The novel system allows for the application of pressure that may facilitate the growth and development of constructs needed to produce a tissue-engineered vascular graft. PMID: 19995361 [PubMed - as supplied by publisher] |
| Hydrophobic-Electrostatic Balance Driving the LCST Offset Aggregation-Redissolution Behavior of N-Alkylacrylamide-Based Ionic Terpolymers.
December 10, 2009 at 6:05 am
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| | Hydrophobic-Electrostatic Balance Driving the LCST Offset Aggregation-Redissolution Behavior of N-Alkylacrylamide-Based Ionic Terpolymers. Langmuir. 2009 Dec 8; Authors: López-Pérez PM, da Silva RM, Pashkuleva I, Parra F, Reis RL, San Roman J A series of random terpolymers composed of N-isopropylacrylamide (NIPAAm), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), and N-tert-butylacrylamide (NTBAAm) monomers were synthesized by free radical polymerization. The molar fraction of the negatively charged monomer (AMPS) was maintained constant (0.05) for all studied terpolymer compositions. Turbidity measurements were used to evaluate the influence of the relative amount of NIPAAm and NTBAAm, polymer concentration, and solution ionic strength on the cloud point and redissolution temperatures (macroscopic phase separation). Dynamic light scattering (DLS) was employed to elucidate some aspects regarding the molecular scale mechanism of the temperature-induced phase separation and to determine the low critical solution temperature (LCST). The aqueous solutions of terpolymers remained clear at all studied temperatures; turbidity was only observed in the presence of NaCl. The cloud point temperature (CPT) determined by turbidimetry was found to be systematically much higher than the LCST determined by DLS; nanosized aggregates were observed at temperatures between the LCST and the CPT. Both CPT and LCST decreased when increasing the molar ratio of NTBAAm (increased hydrophobicity). It was found that above a critical molar fraction of NTBAAm (0.25-0.30) the aggregation rate suddenly decreased. Polymers with NTBAAm content lower than 0.25 showed a fast macroscopic phase separation, but the formed large aggregates are disaggregating during the cooling ramp at temperatures still higher than the LCST. On the contrary, polymers with NTBAAm contents above 0.30 showed a slow macroscopic phase separation, and the formed large aggregates only redissolved when LCST was reached. These differences were explained on the basis of a delicate balance between the electrostatic repulsion and the hydrophobic attractive forces, which contribute cooperatively to the formation of metastable nanosized aggregates. PMID: 19994868 [PubMed - as supplied by publisher] |
| "Ethics, Law, Religion and Clinical Translation in the 21st Century"
December 10, 2009 at 6:00 am
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| | "Ethics, Law, Religion and Clinical Translation in the 21st Century" Stem Cells. 2009 Dec 8; Authors: Trounson A PMID: 19998372 [PubMed - as supplied by publisher] |
| Potentials of regenerative medicine for liver disease.
December 10, 2009 at 6:00 am
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| | Potentials of regenerative medicine for liver disease. Surg Today. 2009;39(12):1019-25 Authors: Ogawa S, Miyagawa S Liver transplantation is still the only effective treatment for end-stage liver disease. However, because of the serious worldwide shortage of donated organs, an alternative cellular therapy would be desirable. Animal studies and preclinical trials have indicated that hepatocyte transplantation can serve as an alternative to liver transplantation. Unfortunately, however, the harvesting of hepatocytes is associated with the same problem as organ transplantation, i.e., a lack of a suitable cell source. Therefore, current stem cell technology, which is attempting to establish an unlimited supply of hepatocytes, would facilitate the clinical application of hepatocyte transplantation. This review summarizes current knowledge of embryonic and adult stem cell differentiation into hepatocytes and discusses how liver stem cells could be applied clinically in the future. PMID: 19997795 [PubMed - in process] |
| Regenerative medicine strategies for treatment of neurogenic bladder.
December 10, 2009 at 6:00 am
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| | Regenerative medicine strategies for treatment of neurogenic bladder. Therapy. 2009;6(2):177-184 Authors: Soler R, Fullhase C, Atala A Neurogenic bladder is a general term encompassing various neurologic dysfunctions in the bladder and external urethral sphincter caused by damage or disease. Therapeutic management options fall into the categories of conservative, minimally invasive or surgical. The current standard for surgical management is bladder augmentation using intestinal segments. However, because intestinal tissue possesses different functional characteristics to bladder tissue, numerous complications can ensue. Regenerative medicine uses combinations of cells and/or biomaterials to encourage regeneration of healthy tissue and offers an alternative approach for the replacement of lost or deficient organs, including the bladder. Promising results using the principles of regenerative medicine have already been obtained in children with neurogenic bladder caused by myelomeningocele. Human clinical trials, governed by the US FDA, are ongoing in the USA in both children and adults to further evaluate the safety and efficacy of this technology for regenerating bladders. More studies are in progress and additional advances in this field can be anticipated. PMID: 19997534 [PubMed - as supplied by publisher] |
| Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy.
December 10, 2009 at 6:00 am
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| | Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy. Mol Ther. 2009 Dec 8; Authors: Kazuki Y, Hiratsuka M, Takiguchi M, Osaki M, Kajitani N, Hoshiya H, Hiramatsu K, Yoshino T, Kazuki K, Ishihara C, Takehara S, Higaki K, Nakagawa M, Takahashi K, Yamanaka S, Oshimura M Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies. PMID: 19997091 [PubMed - as supplied by publisher] |
| Generation of Induced Pluripotent Stem Cells by Reprogramming Human Fibroblasts with the Stemgent Human TF Lentivirus Set.
December 10, 2009 at 6:00 am
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| | Generation of Induced Pluripotent Stem Cells by Reprogramming Human Fibroblasts with the Stemgent Human TF Lentivirus Set. J Vis Exp. 2009;(34): Authors: Wu D, Hamilton B, Martin C, Gao Y, Ye M, Yao S In 2006, Yamanaka and colleagues first demonstrated that retrovirus-mediated delivery and expression of Oct4, Sox2, c-Myc and Klf4 is capable of inducing the pluripotent state in mouse fibroblasts.(1) The same group also reported the successful reprogramming of human somatic cells into induced pluripotent stem (iPS) cells using human versions of the same transcription factors delivered by retroviral vectors.(2) Additionally, James Thomson et al. reported that the lentivirus-mediated co-expression of another set of factors (Oct4, Sox2, Nanog and Lin28) was capable of reprogramming human somatic cells into iPS cells.(3) iPS cells are similar to ES cells in morphology, proliferation and the ability to differentiate into all tissue types of the body. Human iPS cells have a distinct advantage over ES cells as they exhibit key properties of ES cells without the ethical dilemma of embryo destruction. The generation of patient-specific iPS cells circumvents an important roadblock to personalized regenerative medicine therapies by eliminating the potential for immune rejection of non-autologous transplanted cells. Here we demonstrate the protocol for reprogramming human fibroblast cells using the Stemgent Human TF Lentivirus Set. We also show that cells reprogrammed with this set begin to show iPS morphology four days post-transduction. Using the Stemolecule Y27632, we selected for iPS cells and observed correct morphology after three sequential rounds of colony picking and passaging. We also demonstrate that after reprogramming cells displayed the pluripotency marker AP, surface markers TRA-1-81, TRA-1-60, SSEA-4, and SSEA-3, and nuclear markers Oct4, Sox2 and Nanog. PMID: 19997062 [PubMed - in process] |
| Inhibition of Functional Hyaluronan-CD44 Interactions in CD133-positive Primary Human Ovarian Carcinoma Cells by Small Hyaluronan Oligosaccharides.
December 10, 2009 at 6:00 am
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| | Inhibition of Functional Hyaluronan-CD44 Interactions in CD133-positive Primary Human Ovarian Carcinoma Cells by Small Hyaluronan Oligosaccharides. Clin Cancer Res. 2009 Dec 8; Authors: Slomiany MG, Dai L, Tolliver LB, Grass GD, Zeng Y, Toole BP PURPOSE: CD44 is one of the most common markers used for identification of highly tumorigenic subpopulations of human carcinoma cells, but little is known about the function of CD44 or its major ligand, hyaluronan, in these cells. The purpose of this study was to investigate the involvement of hyaluronan and its interaction with CD44 in the properties of a tumorigenic subpopulation of primary ovarian carcinoma cells. EXPERIMENTAL DESIGN: A tumorigenic subpopulation was identified in ascites fluids from ovarian carcinoma patients by expression of high CD133 levels. Treatment with small hyaluronan oligosaccharides, which dissociate constitutive hyaluronan polymer-CD44 interactions, was used to test the importance of hyaluronan-CD44 interaction in assembly of multidrug and monocarboxylate transporters and receptor tyrosine kinases in the plasma membrane of cells with high CD133 levels, and in the tumorigenic capacity of the CD133-high subpopulation. RESULTS: Although total CD44 levels were similar in cells with high or low CD133 expression, CD44 was present in close association with transporters, receptor tyrosine kinases, and emmprin (CD147) in the plasma membrane of cells with high CD133 levels. Treatment with small hyaluronan oligosaccharides reduced association of the transporters and receptor tyrosine kinases with CD44 in the plasma membrane, diminished drug transporter activity, and inhibited i.p. tumorigenesis in these cells. CONCLUSIONS: We conclude that hyaluronan-CD44 interaction plays an important role in the properties of highly tumorigenic cells by stabilizing oncogenic complexes in their plasma membrane, and that treatment with hyaluronan-CD44 antagonists provides a logical therapeutic approach for abrogating the properties of these cells. (Clin Cancer Res 2009;15(24):7593-601). PMID: 19996211 [PubMed - as supplied by publisher] | | | 
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